We have found the specific activity of the fatty acid dioxygenase catalyzing the initial step in prostaglandin biosynthesis to be 4 fold greater in guinea pig uteri at the onset of luteolysis than during earlier stages of the estrous cycle. We now propose to establish whether this increased activity represents either an increase in the level of dioxygenase protein or a decrease in the level of an enzyme inhibitor. To discriminate between these possibilities, we first plan to purify from bovine seminal vesicles an H3 acetyl-dioxygenase specifically acetylated with He acetyl-salicylate and prepare anti-dioxygenase serum. We then will use this serum to determine if uterine dioxygenase activities from pigs in different days of the estrous cycle are equivalent immunochemically. If so, we will determine if the increases in uterine dioxygenase levels result from increased rates of protein synthesis or decreased rates of degradation by measuring the rate constants for degradation of H3 leucine-labeled immunoprecipitated enzyme. The effect of 17 beta-estradiol administration on uterine prostaglandin secretion in ewes. As part of the proposed project we will determine if the activity of the uterine endoperoxide reductase which catalyzes the terminal step in formation of the luteolysin PGF2 alpha fluctuates in parallel with that of the fatty acid dioxygenase. A new procedure is proposed to facilitate measurement of the enzymic synthesis of PGF2 alpha from PGH2. The major contribution of this proposed study will be to provide an examination of the role of protein turnover as a regulatory feature of prostaglandin biosynthesis. If 17 beta-estradiol is found to increase uterine prostaglandin synthetase levels, one could begin to extrapolate these data to other tissues. For example the prothrombogenic activity of estrogens could result from an increase in the aggregatory activity of platelets induced in turn by elevated platelet prostaglandin synthetase concentrations.